Oncogenic protein kinases are frequently potential targets for cancer treatment. Examples include ERBB2 amplification in breast cancer, associated with clinical response to antibodies targeting ERBB2 (see Slamon, et al., N. Engl. J. Med., 344, 783-792 (2001)), and KIT or PDGFRA mutations in gastrointestinal stromal tumors, which lead to sensitivity to the KIT/ABL/PDGFR inhibitor imatinib (see Heinrich et al., J. Clin. Oncol., 21, 4342-4349 (2003)). In lung adenocarcinoma, patients with EGFR-mutant tumors experience tumor shrinkage and prolongation in progression-free survival when treated with EGFR inhibitors. See Pao et al., Proc Natl Acad Sci USA 101, 13306-13311 (2004); Paez et aL, Science 304, 1497-1500 (2004); Lynch et al., N. Engl. J. Med., 350, 2129-2139 (2004); Mok, et al., N. Engl. J. Med. 361, 947-957 (2009). Furthermore, EML4-ALK gene fusion-positive lung cancers can be effectively treated with ALK inhibitors. Soda et al., Nature 448, 561-566 (2007); Kwak et al., N Engl J Med 363, 1693-1703). However, these alterations almost exclusively occur in the rare adenocarcinomas of patients who never smoked, but are uncommon in squamous-cell lung cancer, which is almost invariably associated with smoking. Khuder, Lung Cancer 31, 139-148 (2001).
Although previous studies have reported recurrent genetic alterations in squamous-cell lung cancer (see e.g., Bass, Nat Genet. 41, 1238-1242 (2009), no therapeutically tractable targets have so far been identified. Thus, therapeutic options for squamous-cell lung cancer patients remain scarce, as molecularly targeted drugs such as erlotinib, gefitinib, pemetrexed and cetuximab are either poorly active (see Mok, et al., N. Engl. J. Med. 361, 947-957 (2009); Pirker et al., Lancet 373, 1525-1531 (2009)) or contraindicated (e.g. bevacizumab)(see Sandler et al., N Engl J Med 355, 2542-2550 (2006)). These observations emphasize the need for new “druggable” targets in squamous-cell lung cancer patients.